Long-term objectives for several projects dealing with the "bio- organic chemistry of lipid systems" include: a) Conformations of small molecules bound to liposomal and macromolecular assemblies will be examined by the newly-developed "double-13C-labelling method". The method reveals the dihedral angle about C-C bonds for small molecules (e.g. spermidine, a modulator of cell growth) when complexed in solution. Such information (virtually inaccessible by any other current approach) can find wide utility in the rational design of drugs. b) Enzyme-liable liposomal molecules will be synthesized and examined as target drug delivery systems. Thus, molecules will be constructed so as to form liposomes that can be destroyed by a specific enzyme. An encapsulated drug will, therefore, be released preferentially in tissue where the particular enzyme is produced in high levels. Drug specificity, accordingly, is imparted to the drug by virtue of its "shell" rather tan by the drug itself. c) New inhibitors of phospholipase- A2, based on phospholipids bearing substituents on the chains, will be synthesized and examined for inhibitory activity. The project is prompted by preliminary data showing that phospholipase-A2 will not hydrolyze synthetic lipids bearing certain alkyl groups on the first half of the chains. Inhibiting phospholipase-A2 is important because the enzyme-catalyzed liberation of arachidonic acid represents the rate-determining step in the biosynthesis of prostoglandins (mediators in inflammatory reactions and thus involved in arthritis and other conditions). d) New lipid systems, including copper-containing compounds that form liposomal bilayers, will be synthesized and examined for ion/electron transport properties. Ion transport rates will be measured by a "continuous fluorescence method" whereby entry of a proton into a liposome (with concomitant exit of a mental cation) quenches the fluorescence of an encapsulated dye. The goal is to understand trans-membrane movement, of obvious biochemical and pharmacological relevance, via the coupling of synthetic organic and bio-organic methodologies.